Many people with autoimmune diseases experience disease flares in which disease symptoms worsen. These flares often subside for a while, only to return again. Rosenblum et al. sought to understand the immunological basis for this phenomenon using a mouse model of inducible T cell–driven autoimmunity in the skin that resolves spontaneously. Disease induction was accompanied by an initial expansion of effector T cells in the skin that was followed by an expansion of regulatory T cells (Tregs). Although Treg cells were present in the skin before disease induction, they proliferated in response to autoantigen expression and were more potent immune suppressors. Moreover, disease resolution was critically dependent on Treg cells. Treg cells persisted in the skin in high numbers after disease resolution and were better able to control autoimmune symptoms when autoantigens were reexpressed in the skin. These results demonstrate that Treg cells are important regulators of immune homeostasis and may be critical for containing disease flares often seen in autoimmune diseases.